AB1482 SPECIFIC BLOOD MONOCYTE DISTRIBUTION IN HISTIOCYTOSES CORRELATES WITH VASCULAR INVOLVEMENT AND DISEASE ACTIVITY
Authors: J. Razanamahery, M. Samson, J. Guy, J. Racine, C. Row, S. Francois, J. F. Emile, B. Nicolas, F. Cohen, S. Audia, J. Haroche, B. Bonnotte
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Histiocytoses are rare clonal disorders characterized by the proliferation and accumulation of CD68<sup>+</sup> histiocytes in tissues<sup>[1]</sup>. During histiocytosis, circulating monocytes arising from bone marrow progenitors carry most MAP-kinase gene mutations, but only "classical" monocytes can differentiate into tissue histiocytes<sup>[2]</sup>. However, little is known about the circulating monocyte subset distribution in histiocytoses<sup>[3]</sup> and their differences from other myeloproliferative disorders. <h3>Objectives</h3> We aimed to evaluate the circulating monocyte subset distribution in patients with histiocytoses compared to patients with myeloproliferative disorders (Chronic myelomonocytic leukemia (CMML) and essential thrombocythemia (ET)) and healthy donors (HD). <h3>Methods</h3> Peripheral blood cells were obtained from patients diagnosed in Dijon University hospital between 2020 and 2021, with histiocytoses (n=17), CMML (n=7), ET (n=7), and from 21 HD at steady state. Monocytes were separated on a CD14/CD16 scattergram into CD14<sup>++</sup>/CD16<sup>−</sup> (classical), CD14<sup>++</sup>/CD16<sup>+</sup> (intermediate), and CD14<sup>+</sup>/CD16<sup>++</sup> (non-classical) subsets after stained cell separation. <h3>Results</h3> During histiocytoses, an increase in "classical" monocytes was observed, compared to ET (p= 0.01) while "intermediate" (vs. ET; p= 0.02) and "non-classical" monocytes (vs. HD; p= 0.04) were decreased. The distribution of monocyte subsets in histiocytoses was close to that in CMML and homogenous among the different type of histiocytoses. Compared to CMML patients, clonal hematopoiesis in patients with histiocytoses was associated with a decrease in "classical" monocytes (87.50% vs. 97%; p= 0.002), with an increase in intermediate and "non-classical" monocytes: 5% vs. 2.5% (p= 0.03) and 4% vs. 0.5% (p= 0.01), excepted when MAP-kinase mutation was considered, as monocyte distribution was similar. Patients with vascular involvement (6 ECD including 5 <i>BRAF</i><sup><i>V600E</i></sup>, 1 RDD) had an increase in classical monocytes (96.00% [92.0-96.0] vs. 86.00% [82.5%-92.0%; p=0.008) and a decrease in "non-classical" monocytes (1.00% [1.0-2.0] vs. 5.00% [3.50-9.50]; p=0.007). The correlation between "non-classical" monocytes &lt;4% and vascular involvement was confirmed by Pearson model (0.648; IC95%[0.25-0.86]; p=0.005). Histiocytoses patients achieving a metabolic response had a lower percentage of "intermediate" monocytes (3.5% [2.00-5.00] vs. 7.0% [4.00-13.00]; p= 0.04) and lower CRP levels (3.0 [1.1-8.75] vs. 33.65 [5.33-59.5] mg/L; p=0.04). The only factor influencing the monocytes subset repartition (for "classical" monocytes) was the presence of clonal hematopoiesis (ß coefficient: -10.78; 95%CI [-16.83 to -4.737]; p=0.002) in patients with histiocytoses. <h3>Conclusion</h3> The monocytes subset distribution is singular in histiocytoses compared to other myeloproliferative neoplasms and is influenced by clonal hematopoiesis. The decrease in the "non-classical" subset could represent a surrogate marker of vascular involvement, while the decrease of the intermediate fraction is associated with a metabolic response. <h3>References</h3> [1] Emile, J.-F. <i>et al.</i> Histiocytosis. <i>Lancet</i> (2021) doi:10.1016/S0140-6736(21)00311-1. [2] Milne, P. <i>et al.</i> Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults. <i>Blood</i><b>130</b>, 167–175 (2017). [3] Papo, M. <i>et al.</i> Immune phenotyping of Erdheim-Chester disease through mass cytometry highlights decreased proportion of non-classical monocytes and increased proportion of Th17 cells. <i>Ann Rheum Dis</i><b>79</b>, 1522–1524 (2020). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.